Treatment of urinary tract infection



United States Patent ABSTRACT OF THE DISCLOSURE Crystalline nitrofurantoin of a surface area from 120 cm. gm. to 1000 cm. /gm. will maintain efficacy in treat ing urinary tract infections while substantially reducing the nausea and emesis associated with that drug.

3,401,221 Patented Sept. 10, 1968 of passing through a 50 US. mesh screen but not through a 400 US. mesh screen, are especially adapted to reduction of nausea and emesis upon oral administration without impairment of efiicacy. When nitrofurantoin of the crystal dimensions stated above is administered to a host, effective urinary tract concentration is secured without manifestation of nausea and emesis. The results attained pursuant to a 100 mg. peroral dose in capsule form of the nitroufurantoin crystal of this invention are set forth in the following Table I.

It is readily apparent from the foregoing table that the 50-400 mesh size of nitrofurantoin, a convenient manner of designating crystal size, presents effective urinary concentration of drug and that within that range the 80- 200 mesh size is preferred for optimal performance.

A further delineation of the reduced nausea-emesis propensity present within the crystal size range of nitro- TABLE I Average Average Average Average Average maximum time of maximum time max. N itroiurantoin, 100 mg. capsule total percent maximum urinary urinary percent excreted in percent cone. cone. excreted a 2-hour excretion, attained, attained,

period hours mg./l. hours 50-60 mesh (120-144 cmJ/gm.) 19. 6 8.3 4. 9 83 5. 5 80-120 mesh (195-290 omfi/gm.) 29. 8 12. 9 4. 6 124 5. 0 140-200 mesh (340-485 cmJ/gm.) 32. 3 16. 6 3.8 159 4. 1 200400 mesh (485-970 emJ/gm.) 35. 4 17. 8 3. 6 156 3. 4 Commercial 100 mg. Nitroiurantoiu tablet (ca. 4,000 cmJ/gm.) 36. 1 20. 0 3. 6 151 3. 0

This invention relates to the therapy of urinary tract infection. More particularly it is concerned with improvements in the treatment of urinary tract infection with nitrofurantoin.

In little over a decade nitrofurantoin has come to 0ccupy a leading role in the treatment of infections of the urinary tract. Its widespread use in this respect has been attended with a minimum of side effects. Nonetheless, in common with other widely used therapeutic agents, its use has provoked side effects whose alleviation would be welcomed by the medical practitioner. The most vexing side effect occasioned through the use of nitrofurantoin is that of nauesea and emesis which occurs in a relatively minor proportion of those to whom it is administered. Various attempts to mitigate this problem through reduced dosage regimens, controlled diet or enteric coating of tablets containing it have not been wholly satisfactory thus depriving a relatively minor but nevertheless significant number of its benefits.

It is an object of this invention to provide nitrofurantoin in a form designed to substantially negate the elicitation of nausea and emesis sometimes attendant to its use without impairment of its efficacy.

It is a further object of this invention to provide nitrofurantoin of a crystal size which is readily secured and which is readily formulated in suitable dosage form,

It is a still further object of this invention to provide crystalline nitrofurantoin in a particular crystal size which is substantially devoid of the nausea-emesis drawback sometimes encountered upon its use.

In accordance with the aforestated objects it has been discovered that crystals of nitrofurantoin having a surface area ranging from about 120 cm. /gm. to about 1000 cm. /gm., being substantially in cubic form and capable furantoin of this invention is evoked through the administration of a 10 mg./kg. dose thereof to dogs, a very emetic sensitive species, The results of such administration is shown in Table II below:

TABLE II Percent of dogs Nitrofurantoin crystals: that vomited 50-60 mesh (300-250,:1.) 0 80-120 mesh (180-120 r) 6.3 140-200 mesh (10075,u) 15.6 200-400 mesh (-40,:t) 37.5

It is readily apparent from the foregoing table that the larger size nitrofurantoin is least provocative of emesis again pointing to the -200 mesh size as the preferred embodiment of this invention to secure maximal urinary concentration and minimal nausea and emesis.

The crystal size of nitrofurantoin contemplated in this invention may be readily secured by saturating an appropriate solvent such as nitromethane therewith, advan tageously at elevated temperature, and allowing crystallization to take place spontaneously preferably on cooling slowly, or, if it is desired to hasten the process, a seed crystal may be introduced, until a sufiicient crop is secured. The deposited crop is filtered, dried, ground if necessary, and screened to obtain the desired crystal size range.

For convenient administration the nitrofurantoin crystal size of this invention is preferably composed into capsules using suitable dispersants and excipients such as milk sugar and dextrose to insure even distribution and dispersion. Other acceptable pharmaceutical dosage forms such as a thixotropic suspension which will preserve the integrity of the crystal size may be employed.

What is claimed is:

1.- Crystalline nitrofurantoin having essentially a surface area ranging from 195 cnL gm. to 485 cm. /gm.

2. A pharmaceutical preparation in unit capsule dosage form containing 100 mg. of crystalline nitrofurantoin having essentially a surface area ranging from 195 cm. /gm. to 485 cmfi/gm.

4 References Cited Wilson and Jones: American Drug Index for 1962, pp. 334, 335 and 518 (1962).

5 ALBERT T. MEYERS, Primary Examiner.

I. D. GOLDBERG, Assistant Examiner. 

